Advances in Biochemistry 2020; 8(2): 38-44 http://www.sciencepublishinggroup.com/j/ab doi: 10.11648/j.ab.20200802.12 ISSN: 2329-0870 (Print); ISSN: 2329-0862 (Online) Manifestation of Functional Defects of Nervous System in Upf3 Mutants Drosophila melanogaster at Larval and Adult Stages Sanusi Ahmed Jega 1, 5 , Ahmed Adebowole Adedeji 1, 2 , Marta Vicente-Crespo 3, 4, * 1 Faculty of Biomedical Science, Kampala International University, Ishaka-Bushenyi, Uganda 2 Foresight Institute of Research and Translation, Ibadan, Nigeria 3 Institute of Biomedical Research, Kampala International University, Ishaka-Bushenyi, Uganda 4 African Population and Health Research Center, Nairobi, Kenya 5 Department of Biochemistry, Faculty of Life Sciences, Kebbi State University of Science and Technology, Aliero, Nigeria Email address: * Corresponding author To cite this article: Sanusi Ahmed Jega, Ahmed Adebowole Adedeji, Marta Vicente-Crespo. Manifestation of Functional Defects of Nervous System in Upf3 Mutants Drosophila melanogaster at Larval and Adult Stages. Advances in Biochemistry. Vol. 8, No. 2, 2020, pp. 38-44. doi: 10.11648/j.ab.20200802.12 Received: March 30, 2020; Accepted: April 13, 2020; Published: May 14, 2020 Abstract: Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that cleans the system from possible harmful proteins and also regulates up to 10% of normal RNAs. The essential player proteins in the NMD (core NMD factors) are Upf1, Upf2, and Upf3. Mutation of any of these NMD factors cause ranges of effects in the development of various organisms. In humans, mutation of Upf3 was associated with neurodegenerative disorders, which include: attention deficit, schizophrenia autism, and intellectual disability. Using functional genetics approach and behavioral analysis methods we examined the loss of function effects of Upf3, in the nervous system function of a Drosophila melanogaster. We observed certain nervous system functional defects in homozygous Upf3 mutants. The embryos exhibited reduced and delayed hatching, the larvae manifested defects in motor function and the adults showed reduced climbing ability, defective short term memory, and learning, and notably, the adult life span was also reduced. This work has further revealed the prospect of Upf3 as a player gene for consideration in the management of neurodegenerative diseases. We explored this using Drosophila melanogaster as a model organism to mimic and study the neurodegenerative traits observed in the patients suffering from Upf3 mutation. Likewise, it suggests a further investigation into the mechanistic insight for the roles of Upf3 in both early and late CNS development. Keywords: Nonsense-mediated mRNA Decay, NMD Factors, Organismal Development, Neurodegenerative Behaviors, Drosophila melanogaster 1. Introduction Nonsense mediated mRNA decay (NMD) is a posttranscriptional regulatory pathway that controls the quality of mRNAs and also shapes the normal transcriptome [1]. NMD is triggered by conditions such as the presence of premature termination codon (PTC) on RNA, long 3'- untranslated region (3'UTR) and upstream open reading frame (uORF) [2]. NMD pathway operates via the coordination of some functional proteins termed NMD factors. Their structural designs allow them to identify and bind to a target mRNA for regulation. The core factors of the NMD machinery are the Up-frame shift suppressor (Upf) proteins (Upf1, Upf2, and Upf3) that are conserved in all eukaryotes studied [3]. Also crucial for the process are the Suppressor with morphological effect on genitalia (SMG) proteins; SMG1 and SMG5-9 [4]. Several lines of evidence suggest that NMD factors play various roles in the development of nervous system. For example in embryos of zebrafish, there was impaired eye